The long term objective of the proposed program is to elucidate the role of types and levels of dietary fat in colon carcinogenesis. The specific aims are: (1) to compare the dose-response effect of 5, 10, 12.5, 15 and 20% corn oil or lard on the initiation and promotional stages of colon cancer; (2) to determine the threshold level at which types of dietary fat exerts measurable effects on colon cancer; (3) to assess the effect of types of dietary fat during the initiation stage of colon carcinogenesis using carcinogen metabolism and DNA methylation as indicators; (4) to assess the effect of types of fat during the promotional stage using colonic secondary bile aids and 7Alpha-dehydroxylase and colonic mucosal ornithine decarboxylase (ODC) activity as indicators, and (5) to determine the effect of types and levels of fat on prostaglandins and prostaglandin synthetase activity of colon tumors. From these it is possible to determine the mechanism by which the types of dietary fat affect the colon tumor initiation and promotion. At 35 days of age, groups of male F344 rats will be fed the diets containing 5, 10, 12.5, 15 and 20% corn oil or lard (for initiation study) or the diets containing 5% corn oil or lard (for promotion study) and continued on these diets during and 3 days after carcinogen treatment. At 56 days of age, all animals except vehicle controls will receive a single s.c. dose of azoxymethane (AOM) (20 mg/kg bw). Three days after AOM or vehicle (normal saline) treatment, all groups of animals intended for initiation study will be transferred to their respective 5% fat diets and continued until the termination of the experiment, whereas the animals intended for promotion study will be transferred to their respective 5% 10, 12.5, 15 and 20% corn oil or lard diets and continued on these diets until the termination of the experiment, which is 32-34 weeks after AOM injection. Some of the animals fed various diets and intended for initiation study will be used for the determination of the activities of hepatic and colonic mucosal enzymes involved in AOM metabolism and of hepatic and colonic mucosal DNA methylation. Fecal bile acids, colonic 7Alpha-dehydroxylase and colonic mucosal ODC levels will be determined in animals intended for promotion study. Prostaglandin and prostaglandin synthetase activity will be determined in colon tumors.